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Organ donation after circulatory determination of death (DCDD) has contributed significantly to the donor pool in several countries, most commonly being category III-controlled donations. This document, prepared by a multidisciplinary group of experts, describes the feasibility of category III DCDD in India, in view of the January 2023 Supreme Court (SC) judgment simplifying the process of withdrawal of life-sustaining treatment (WLST). The paper discusses the concept and types of futility of care, how to elicit patients values and wishes, outlines its determination in several clinical situations and the process of WLST in such cases, in accordance with the SC judgement. The judgement mandates evaluation for futility of care by the primary and secondary medical boards before intimation to the judicial magistrate and WLST. The paper also discusses the use of new and upcoming organ preservation techniques and technologies in various organ transplants and outcomes of such transplants. We have also reviewed international best practices in cDCDD, discuss the ethical, medical, legal, economic, procedural, and logistic challenges in India and outline a path for DCDD in India. The manuscript discusses and compares the timing and location of WLST, consent for antemortem measures, no-touch period, and the possibility of stand-down and return to the intensive care unit (ICU) without donation. Further clarifications of aspects such as ante-mortem measures and do-not attempt resuscitation (DNAR) may be required during implementation of the judgement in some situations.

Abstract The cytoskeleton is a complex network of interconnected biopolymers consisting of actin filaments, microtubules, and intermediate filaments. These biopolymers work in concert to transmit cell-generated forces to the extracellular matrix required for cell motility, wound healing, and tissue maintenance. While we know cell-generated forces are driven by actomyosin contractility and balanced by microtubule network resistance, the effect of intermediate filaments on cellular forces is unclear. Using a combination of theoretical modeling and experiments, we show that vimentin intermediate filaments tune cell stress by assisting in both actomyosin-based force transmission and reinforcement of microtubule networks under compression. We show that the competition between these two opposing effects of vimentin is regulated by the microenvironment stiffness. These results reconcile seemingly contradictory results in the literature and provide a unified description of vimentin’s effects on the transmission of cell contractile forces to the extracellular matrix.

Abstract In interphase nuclei, chromatin forms dense domains of characteristic sizes, but the influence of transcription and histone modifications on domain size is not understood. We present a theoretical model exploring this relationship, considering chromatin-chromatin interactions, histone modifications, and chromatin extrusion. We predict that the size of heterochromatic domains is governed by a balance among the diffusive flux of methylated histones sustaining them and the acetylation reactions in the domains and the process of loop extrusion via supercoiling by RNAPII at their periphery, which contributes to size reduction. Super-resolution and nano-imaging of five distinct cell lines confirm the predictions indicating that the absence of transcription leads to larger heterochromatin domains. Furthermore, the model accurately reproduces the findings regarding how transcription-mediated supercoiling loss can mitigate the impacts of excessive cohesin loading. Our findings shed light on the role of transcription in genome organization, offering insights into chromatin dynamics and potential therapeutic targets.

The distinct presence of a central atom surrounded by eight ligands leads to higher light absorption and charge carrier mobility in perovskite materials. The peculiar nature of the structure inspires all the scientists and researchers to work more in sustainable applications, such as solar cells, light emitting diodes, transistor and biosensors. The capability of perovskite material in detecting smaller molecules such as O2, NO2 and CO2 is higher. Therefore, several biosensors are demonstrated based on the perovskite nanomaterial to various chemical and biological species with both solid and solution states. The immense sources of research articles thrived the author, to review the perovskite nanomaterials in the dimension of biosensor application extensively. This review covers major three areas of perovskite nanomaterial, such as components and characteristics of biosensors, properties and preparation of perovskite materials and application and research trends of perovskite nanostructure biosensor.

Development of de novo donor-specific anti-HLA antibody (dnDSA) is associated with poor graft survival in adults. However, there is a paucity of data about its prevalence and outcome in Indian children. We retrospectively assessed the proportion and spectrum of dnDSA and its outcome on antibody-mediated rejection (ABMR) and graft function. Children ≤18 years who were transplanted between November 2016 and October 2019 were included in this study. Pretransplant donor-specific antibody (DSA) was screened by complement-dependent cytotoxicity, flow cytometry crossmatch, and single antigen bead (SAB) class I and II by Luminex platform. Either antithymocyte globulin or basiliximab was used as induction. Tacrolimus, mycophenolate, and prednisolone were used for the maintenance of immunosuppression. SAB screening was done at 1, 3, 6 months, and yearly in seven children and at the time of acute graft dysfunction in eight. Mean fluorescence intensity ≥1000 was considered positive. Protocol biopsies were done at 3, 6, and 12 months and annually thereafter in seven children. Fifteen children, all males with a median age (interquartile range) of 13 years (11; 15.5) were analyzed. Only one child had pretransplant DSA who developed dnDSA posttransplant. Overall, 8 (53%) developed dnDSA over a median follow-up of 18 months. Seven (87%) had Class II, one Class I and 3 (37%) both Class I and II. Six had dQ and two had DR. All children with dnDSA had ABMR, of these two had subclinical rejection. DSAs persisted despite treatment, though graft function improved. Children with DSA and ABMR had lower graft function than those without DSA. The proportion of dnDSA was high in our study, majority against DQ. The detection of dnDSA prompted early diagnosis and treatment of ABMR.

Abstract Srs2 is an Sf1a helicase that helps maintain genome stability in Saccharomyces cerevisiae through its ability to regulate homologous recombination. Srs2 downregulates HR by stripping Rad51 from single–stranded DNA, and Srs2 is also thought to promote synthesis–dependent strand annealing by unwinding D–loops. However, it has not been possible to evaluate the relative contributions of these two distinct activities to any aspect of recombination. Here, we used a structure–based approach to design an Srs2 separation–of–function mutant that can dismantle Rad51–ssDNA filaments but is incapable of disrupting D–loops, allowing us to assess the relative contributions of these pro– and anti–recombinogenic functions. We show that this separation–of–function mutant phenocopies wild–type SRS2 in vivo, suggesting that the ability of Srs2 to remove Rad51 from ssDNA is its primary role during HR.

Purpose: To report the incidence and risk factors for any ROP and type 1 ROP and treatment outcomes of type 1 ROP. Methods and Material: Infants born in our hospital with gestational age (GA) of < 34weeks or birth weight (BW) < 2000g were screened for ROP and treated if type 1 ROP developed. Incidence of any ROP and type 1 ROP were calculated. Several variables were evaluated by univariate and multivariate analyses to find their significance for any ROP and type 1 ROP. Results of treatment for type 1 ROP are reported. Results: Out of 263 infants screened, 64 (24.3%) developed any ROP and 15(5.7%) type 1 ROP. All the eyes with type 1 ROP showed complete regression after treatment. Multivariate analysis showed that; infants with GA of 31-34 weeks had significantly less any ROP (P=0.002) and type 1 ROP (p= 0.020) versus infants of GA ≤30w. Infants with BW≥1501g had less any ROP (P=0.025) and less type 1 ROP (P=0.018) versus infants with BW ≤1250g. Infants with BW 1251g to 1500g had less type 1 ROP versus infants with BW≤1250g. (P=0.042) and females had significantly less type 1 ROP (P= 0.012) versus male infants. Conclusions: The incidence of any ROP and type 1 ROP were relatively low in our study. Type 1 ROP regressed completely in all eyes after treatment. GA, BW and gender were significant factors for any ROP and type 1 ROP.

Abstract Immune cells, such as macrophages and dendritic cells, can utilize podosomes, mechanosensitive actin-rich protrusions, to generate forces, migrate, and patrol for foreign antigens. Individual podosomes probe their microenvironment through periodic protrusion and retraction cycles (height oscillations), while oscillations of multiple podosomes in a cluster are coordinated in a wave-like fashion. However, the mechanisms governing both the individual oscillations and the collective wave-like dynamics remain unclear. Here, by integrating actin polymerization, myosin contractility, actin diffusion, and mechanosensitive signaling, we develop a chemo-mechanical model for podosome dynamics in clusters. Our model reveals that podosomes show oscillatory growth when actin polymerization-driven protrusion and signaling-associated myosin contraction occur at similar rates, while the diffusion of actin monomers drives wave-like coordination of podosome oscillations. Our theoretical predictions are validated by different pharmacological treatments and the impact of microenvironment stiffness on chemo-mechanical waves. Our proposed framework can shed light on the role of podosomes in immune cell mechanosensing within the context of wound healing and cancer immunotherapy.

The discovery of intrinsic magnetic topological order in MnBi2Te4 has invigorated the search for materials with coexisting magnetic and topological phases. These multiorder quantum materials are expected to exhibit new topological phases that can be tuned with magnetic fields, but the search for such materials is stymied by difficulties in predicting magnetic structure and stability. Here, we compute more than 27,000 unique magnetic orderings for more than 3000 transition metal oxides in the Materials Project database to determine their magnetic ground states and estimate their effective exchange parameters and critical temperatures. We perform a high-throughput band topology analysis of centrosymmetric magnetic materials, calculate topological invariants, and identify 18 new candidate ferromagnetic topological semimetals, axion insulators, and antiferromagnetic topological insulators. To accelerate future efforts, machine learning classifiers are trained to predict both magnetic ground states and magnetic topological order without requiring first-principles calculations.

Altered microarchitecture of collagen type I is a hallmark of wound healing and cancer that is commonly attributed to myofibroblasts. However, it remains unknown which effect collagen microarchitecture has on myofibroblast differentiation. Here, we combined experimental and computational approaches to investigate the hypothesis that the microarchitecture of fibrillar collagen networks mechanically regulates myofibroblast differentiation of adipose stromal cells (ASCs) independent of bulk stiffness. Collagen gels with controlled fiber thickness and pore size were microfabricated by adjusting the gelation temperature while keeping their concentration constant. Rheological characterization and simulation data indicated that networks with thicker fibers and larger pores exhibited increased strain-stiffening relative to networks with thinner fibers and smaller pores. Accordingly, ASCs cultured in scaffolds with thicker fibers were more contractile, expressed myofibroblast markers, and deposited more extended fibronectin fibers. Consistent with elevated myofibroblast differentiation, ASCs in scaffolds with thicker fibers exhibited a more proangiogenic phenotype that promoted endothelial sprouting in a contractility-dependent manner. Our findings suggest that changes of collagen microarchitecture regulate myofibroblast differentiation and fibrosis independent of collagen quantity and bulk stiffness by locally modulating cellular mechanosignaling. These findings have implications for regenerative medicine and anticancer treatments.

MXenes are a rapidly-expanding family of 2D transition metal carbides and nitrides that have attracted attention due to their excellent performance in applications ranging from energy storage to electromagnetic interference shielding. Numerous other electronic and magnetic properties have been computationally predicted, but not yet realized due to the experimental difficulty in obtaining uniform surface terminations (Tx), necessitating new design approaches for MXenes that are independent of surface terminations. In this study, we distinguished the contributions of surface and sub-surface Ti atoms to the electronic structure of four Ti-containing MXenes (Ti2CTx, Ti3C2Tx, Cr2TiC2Tx, and Mo2TiC2Tx) using soft x-ray absorption spectroscopy. For MXenes with no Ti atoms on the surface transition metal layers, such as Mo2TiC2Tx and Cr2TiC2Tx, our results show minimal changes in the spectral features between the parent MAX phase and its MXene. In contrast, for MXenes with surface Ti atoms, here Ti3C2Tx and Ti2CTx, the Ti L-edge spectra are significantly modified compared to their parent MAX phase compounds. First principles calculations provide similar trends in the partial density of states derived from surface and sub-surface Ti atoms, corroborating the spectroscopic measurements. These results reveal that electronic states derived from sub-surface M-site layers are largely unperturbed by the surface terminations, indicating a relatively short length scale over which the Tx terminations alter the nominal electron count associated with Ti atoms and suggesting that desired band features should be hosted by sub-surface M-sites that are electronically more robust than their surface M-site counterparts.

Vaccine-induced thrombotic thrombocytopenia (VITT) has been recently linked with coronavirus disease (COVID-19) vaccines. It becomes crucial for the transplant communities to have a rigorous approach for accepting VITT donors, as the reports of such transplantation have been associated with thrombotic complications, graft loss, and deaths. The magnitude of facing a VITT donor in transplantation practices is unknown and also the management protocol. However, as per the limited data, it is better to avoid such transplants, and in the case of emergency transplants, the risk-benefit ratio should be weighed. All transplantation from VITT donors should be appropriately counseled before procurement. The organs should undergo deliberate examination for functionality by clinical, laboratory, and radiological parameters. In doubtful cases, a preimplantation biopsy is mandated to rule out any thrombosis. VITT donors are suggested to be treated with newer oral anti-coagulation and intravenous immunoglobulin. Platelet transfusion is best avoided in a VITT donor. There is no established protocol for any modification in surgical procedure, anesthesia, or immunosuppressive medicines in the recipients. The recipients should undergo extensive clinical and laboratory monitoring for any possible complications. No prophylactic therapy is recommended at present but candidates with a history of any COVID-19 vaccine within 30 days, should be avoided. In summary, the evidence for diagnosis and management of VITT donors is based only on a few reports, but with current knowledge, it is advisable to take a multidisciplinary approach to assess all benefits and risks before accepting or discarding organs.

Gap formation in the vasculature underpins immune and tumour cell infiltration. Here the authors propose a chemo-mechanical model to analyse how feedback between mechanosensitive signalling, active cellular forces and adhesion governs the breakdown, recovery, and integrity of endothelial junctions.

Outcomes of severe acute respiratory syndrome coronavirus 2 in kidney transplant recipients (KTR) compared with matched cohort are certainly lacking for different pandemic waves and geographic regions. In this single-center retrospective study of coronavirus disease-2019 (COVID-19) cases admitted during March 26, 2021 to June 7, 2021, a propensity-matched analysis in a 1:1 ratio was performed to compare the clinical profile and outcomes between KTR and non-KTR. A Cox proportional hazard model from the whole study population to analyze risk factors for severe disease and mortality was calculated. We identified 1052 COVID-19 cases, of which 107 (10.1%) were KTR. In propensity-matched analysis, KTR had higher fever (81.6 % vs. 60%; P = 0.01), lymphopenia (30% vs. 11.7%; P = 0.02), higher neutrophil-to-lymphocyte ratio (43.3% vs. 25%; P = 0.05), and acute kidney injury (66.6% vs. 36.7%; P = 0.001). In Kaplan–Meier survival analysis, there was no difference in mortality or severity of COVID-19. In Cox hazard proportional analysis, the European cooperative oncology group (ECOG) score of 1 to 2 [Hazard ratio (HR) 95% lower confidence interval (CI), upper CI = 4.9 (1.8–13.5); P 2 [HR = 20 (7.5, 54.7); P

Introduction: Telemedicine represents an innovative but untested approach to maintain patient care and reduce the risk of COVID-19 exposure to patients, health-care workers, and the public. In this study, we evaluated the applicability and efficacy of telemedicine in a kidney transplant recipient (KTR) cohort in COVID 19 era. Materials and Methods: An observational cohort study was conducted at a tertiary-care public-sector kidney disease institute in western India between March and September 2020. We evaluated the reasons, modes, and outcomes of patient contacts by telemedicine in the KTR cohort. We also evaluated the utility of telemedicine across three age groups. Results: Of 840 participants, whose mean age was 38.78 ± 12.39 years, male to female ratio was 4:1. The most common mode of communication was WhatsApp (653, 77.7%) followed by in-person surrogates (126, 15%). Acceptability of telemedicine was significantly better in younger and middle-age groups (P < 0.00001) compared to the elderly. Request for drug delivery (n = 756) was the most common reason for contact overall and managed through postal parcels. KTRs (n = 200) and donors (n = 75) were evaluated for medical illnesses. The most common medical reasons for contact were for febrile illness (n = 120) and graft dysfunction (n = 60). COVID-19-related disease was diagnosed and managed in 80 KTRs and 2 donors. COVID-19 updates were given to all contacts. Conclusion: Telemedicine is underutilized in the care of the KTR cohort. Telemedicine can be used across all ages although it's best suited for young and middle age groups. The impact of telemedicine on short- and long-term patient outcomes is unclear and warrants further study.

Coronavirus disease 2019 (COVID-19) vaccine efficacy, especially against severe disease is known to wane over time. We examined current knowledge of COVID-19 vaccine booster dose in solid organ transplant recipients (SOTR). We have systematically searched PubMed, EMBASE, MEDLINE, Scopus and Google Scholar with the following MeSH terms: “SARS-CoV-2 vaccine,” or “COVID-19 vaccine,” and “organ transplantation” and “booster” or “third dose.” This review article examines a number of studies including guidelines from professional societies examining the safety as well as increased immunogenicity of a booster dose among SOTR. Equitable distribution of vaccines across the globe is the need of the hour. While some countries are well into the booster dose phase, the lower-income countries are languishing behind with primary doses for their health workers. Available reports suggest less efficacy of COVID-19 vaccine in SOTR suggesting booster dose for them. Several studies highlighted the safety and efficacy of COVID-19 vaccines booster dose among SOTR. SOTR should also continue to adhere to all safety and COVID-19 appropriate behaviors. There is a growing need for alternative strategies to improve protection. As Omicron cases rise around the world, India announced that COVID-19 vaccination for children aged 15–18 years and “precautionary (booster) doses” would be administered to healthcare and frontline workers and people above 60 years of age with comorbidities from January 2022. In near future, with increased availability of vaccinations, all SOTR will have access to booster dose in a phased manner.

From the context of organ donation, COVID-19 vaccine-induced thrombotic thrombocytopenia (VITT) is important as there is an ethical dilemma in utilizing versus discarding organs from potential donors succumbing to VITT. This consensus statement is an attempt by the National Organ and Tissue Transplant Organization (NOTTO) apex technical committees, India, to formulate the guidelines for deceased organ donation and transplantation in relation to VITT to help in appropriate decision-making. VITT is a rare entity, but a meticulous approach should be taken by the organ procurement organization's (OPO) team in screening such cases. All such cases must be strictly notified to the national authorities (NOTTO) as a resource for data collection and ensuring compliance with protocols in the management of adverse events following immunization. Organs from any patient who developed thrombotic events up to 4 weeks after adenoviral vector-based vaccination should be considered to be linked to VITT and investigated appropriately. The viability of the organs must be thoroughly checked by the OPO, and the final decision in relation to organ use should be decided by the expert committee of the OPO team consisting of a virologist, a hematologist, and a treating team. Considering the organ shortage, in case of suspected/confirmed VITT, both clinicians and patients should consider the risk‒benefit equation based on limited experience. An appropriate written informed consent of potential recipients and family members should be obtained before the transplantation of organs from suspected or proven VITT donors.

Graft loss and rejections (acute/chronic) continue to remain important concerns in long-term outcomes in kidney transplant despite newer immunosuppressive regimens and increased use of induction agents. Global guidelines identify the risk factors and suggest a framework for management of patients at different risk levels for rejection; however, these are better applicable to deceased donor transplants. Their applicability in Indian scenario (predominantly live donor program) could be a matter of debate. Therefore, a panel of experts discussed the current clinical practice and adaptability of global recommendations to Indian settings. They also took a survey to define risk factors in kidney transplants and provide direction toward evidence- and clinical experience-based risk stratification for donor/recipient and transplant-related characteristics, with a focus on living donor transplantations. Several recipient related factors (dialysis, comorbidities, and age, donor-specific antibodies [DSAs]), donor-related factors (age, body mass index, type – living or deceased) and transplantation related factors (cold ischemia time [CIT], number of transplantations) were assessed. The experts suggested that immunological conflict should be avoided by performing cytotoxic cross match, flow cross match in all patients and DSA-(single antigen bead) whenever considered clinically relevant. HLA mismatches, presence of DSA, along with donor/recipient age, CIT, etc., were associated with increased risk of rejection. Furthermore, the panel agreed that the risk of rejection in living donor transplant is not dissimilar to deceased donor recipients. The experts also suggested that induction immunosuppression could be individualized based on the risk stratification.

Contractile cells can reorganize fibrous extracellular matrices and form dense tracts of fibers between neighboring cells. These tracts guide the development of tubular tissue structures and provide paths for the invasion of cancer cells. Here, we studied the mechanisms of the mechanical plasticity of collagen tracts formed by contractile premalignant acinar cells and fibroblasts. Using fluorescence microscopy and second harmonic generation, we quantified the collagen densification, fiber alignment, and strains that remain within the tracts after cellular forces are abolished. We explained these observations using a theoretical fiber network model that accounts for the stretch-dependent formation of weak cross-links between nearby fibers. We tested the predictions of our model using shear rheology experiments. Both our model and rheological experiments demonstrated that increasing collagen concentration leads to substantial increases in plasticity. We also considered the effect of permanent elongation of fibers on network plasticity and derived a phase diagram that classifies the dominant mechanisms of plasticity based on the rate and magnitude of deformation and the mechanical properties of individual fibers. Plasticity is caused by the formation of new cross-links if moderate strains are applied at small rates or due to permanent fiber elongation if large strains are applied over short periods. Finally, we developed a coarse-grained model for plastic deformation of collagen networks that can be employed to simulate multicellular interactions in processes such as morphogenesis, cancer invasion, and fibrosis.

The aim was to describe inpatients with COVID-19 empirically prescribed heparinoid anticoagulants and compare resource utilization between prophylactic/low-dose and therapeutic/high-dose groups. Methods: This retrospective observational study used real-world data from 880 US hospitals in the PINC AI™ Healthcare Database during 4/1/2020–11/30/2020. Descriptive analysis was used to characterize patients. Multivariable regression was used to evaluate intensive care unit (ICU) admissions, length of stay (LOS), mortality, and costs by anticoagulation dose group, adjusting for cohort characteristics. Among 122,508 inpatients, 29,225 (23.9%) received therapeutic/high-dose, and 93,283 (76.1%) received prophylactic/low-dose anticoagulation. The high-dose group had more comorbidities and worse laboratory values compared with low-dose. Respectively, ICU admission rates were 36.7% and 19.1% and LOS median (Q1, Q3) was 8 (5, 15) and 5 (3, 9) days. In separate adjusted models, high-dose anticoagulation was associated with a 45% increase in odds of ICU admission, 26% increase in odds of in-hospital mortality, 21% longer average LOS, and 28% greater average total cost compared with low-dose (each P

Abstract Here we present a microengineered soft-robotic in vitro platform developed by integrating a pneumatically regulated novel elastomeric actuator with primary culture of human cells. This system is capable of generating dynamic bending motion akin to the constriction of tubular organs that can exert controlled compressive forces on cultured living cells. Using this platform, we demonstrate cyclic compression of primary human endothelial cells, fibroblasts, and smooth muscle cells to show physiological changes in their morphology due to applied forces. Moreover, we present mechanically actuatable organotypic models to examine the effects of compressive forces on three-dimensional multicellular constructs designed to emulate complex tissues such as solid tumors and vascular networks. Our work provides a preliminary demonstration of how soft-robotics technology can be leveraged for in vitro modeling of complex physiological tissue microenvironment, and may enable the development of new research tools for mechanobiology and related areas.